aroA-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractRecombinant attenuated Salmonella enterica serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of aroA, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of aroA dramatically increased the virulence of attenuated Salmonella in mouse models. Mutant bacteria lacking aroA elicited increased levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) after systemic application. A detailed genetic and phenotypic characterization in combination with transcriptomic and metabolic profiling demonstrated that ΔaroA mutants display pleiotropic alterations in cellular physiology and lipid and amino acid metabolism, as well as increased sensitivity to penicillin, complement, and phagocytic uptake. In concert with other immunomodulating mutations, deletion of aroA affected flagellin phase variation and gene expression of the virulence-associated genes arnT and ansB Finally, ΔaroA strains displayed significantly improved tumor therapeutic activity. These results highlight the importance of a functional shikimate pathway to control homeostatic bacterial physiology. They further highlight the great potential of ΔaroA-attenuated Salmonella for the development of vaccines and cancer therapies with important implications for host-pathogen interactions and translational medicine.
CitationaroA-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant. 2016, 7 (5): MBio
The following license files are associated with this item:
- Evaluation of Salmonella enterica serovar Typhimurium and Choleraesuis slyA mutant strains for use in live attenuated oral vaccines.
- Authors: Haneda T, Okada N, Kikuchi Y, Takagi M, Kurotaki T, Miki T, Arai S, Danbara H
- Issue date: 2011 Sep
- Virulence and vaccine potential of Salmonella typhimurium mutants deficient in the expression of the RpoS (sigma S) regulon.
- Authors: Coynault C, Robbe-Saule V, Norel F
- Issue date: 1996 Oct
- Genetic detoxification of an aroA Salmonella enterica serovar Typhimurium vaccine strain does not compromise protection against virulent Salmonella and enhances the immune responses towards a protective malarial antigen.
- Authors: McKelvie ND, Khan SA, Karavolos MH, Bulmer DM, Lee JJ, DeMarco R, Maskell DJ, Zavala F, Hormaeche CE, Khan CM
- Issue date: 2008 Mar
- Deletion of luxS further attenuates the virulence of the avian pathogenic Escherichia coli aroA mutant.
- Authors: Han X, Bai H, Tu J, Yang L, Xu D, Wang S, Qi K, Fan G, Zhang Y, Zuo J, Tian M, Ding C, Yu S
- Issue date: 2015 Nov
- Evaluation of the live vaccine efficacy of virulence plasmid-cured, and phoP- or aroA-deficient Salmonella enterica serovar Typhimurium in mice.
- Authors: Matsui H, Isshiki Y, Eguchi M, Ogawa Y, Shimoji Y
- Issue date: 2015 Feb